Genomics and Proteomics Engineering in Medicine and Biology - Metin Akay

FIGURE 10.5. Continued.

RRM characteristic frequency is a relevant parameter for mutual recognition between biomolecules and is significant in describing the interaction between proteins and their substrates or targets. Therefore, it is concluded that the RRM characteristic frequency may dictate the specificity of the protein interactions [9].

From Figure 10.3d we can observe only one dominant peak corresponding to the common frequency component for the combined group of T-antigen and p53 proteins at f ¼ 0.2021 + 0.048, S/N ¼ 312.36. Analogous results were obtained in the analysis of interactions between T-antigen and pRb proteins. A single

TABLE 10.5 Peak Frequency and Signal-to-Noise Ratio Values of Protein Groups

280 TUMOUR AND TUMOUR SUPPRESSOR PROTEINS

three-component interaction between T-antigen, p53, and pRb proteins can be considered as a crucial condition in the process of brain tumor formation.

Also it can be observed from the two cross-spectral functions of agnoprotein and T-antigen proteins (Figs. 10.4a and 10.4b) that characteristic frequencies of these protein groups are different, leading to the conclusion that agnoprotein and T-antigen protein will not interact with each other (Table 10.5). Interestingly to, the same conclusion was withdrawn after finalizing the experimental study using the T-antigen and agnoprotein [24]. Results of our computational analysis suggest that only a four-component interaction between agnoprotein, T-antigen, p53, and pRb proteins (Fig. 10.4e) gives the same characteristic frequency at f ¼ 0.2021 (characteristic feature of tumor development). Therefore it can be postulated that a possible interaction between agnoprotein and pRb tumor suppressor proteins may lead to the inactivation of pRb functionality that can initiate a process of a tumor formation.

10.3.3. HSP and Tumour Suppressor Protein Interactions

Here 30 HSP sequences, 13 p53 protein sequences, and 9 pRb protein sequences were investigated concerning the understanding of the structure–function relationship within these proteins. A multiple cross-spectral analysis was performed for each selected protein group as well as for their mutual combination using the EIIP values (Figs. 10.7a to 10.7f ). As a result, characteristic frequencies of analyzed protein groups were obtained and are shown in Table 10.6. Also Continuous Wavelet Transform (CWT) was used for the determination of functional active sites of mouse HSP70/HSP90 protein (Fig. 10.8).

Initially the structure–function analysis was applied to a group of 30 HSP sequences, and two peak frequencies were identified in their multiple crossspectrum: f1 ¼ 0.0195 + 0.033 characterizing HSP’s immunoregulatory activity and f2 ¼ 0.4248 + 0.033 (the same frequency was identified for Fibroblast Growth Factor (FGF) proteins in our previous studies [9, 19]) that characterize the ability to regulate cell growth and differentiation (Fig. 10.7a).

The same procedure was repeated with p53 and pRb tumor suppressor proteins (Figs. 10.7b and 10.7d). The p53 tumor suppressor gene is one of the genes most often mutated in human cancers. Its mainly point mutations lead to amino acid substitutions in the central region of the protein and thus cause its abnormal function. The prominent characteristic frequencies of p53 and pRb tumor suppressor proteins were identified at f ¼ 0.4326 + 0.077 and f ¼ 0.4316 + 0.111, respectively.

The similarity of characteristic frequencies of p53 and pRb proteins (Figs. 10.7b and 10.7d) is expected as both p53 and pRb proteins have the same biological function—tumor suppression. Thus, it has been suggested that the frequency f ¼ 0.4316 identified within the RRM analysis be considered as a characteristic feature of the specific biological activity of p53 and pRb proteins—regulation of cells growth and proliferation—and consequently ability to prevent tumor formation.

As was mentioned above in the consensus spectrum of HSPs (Fig. 10.7a), we can observe two peaks with different amplitude ratios. One prominent peak at

FIGURE 10.7. Multiple cross-spectral function of protein groups: (a) HSP proteins, (b) p53 proteins, (c) HSP and p53 proteins, (d) pRb proteins, (e) HSP and pRb proteins, and ( f ) HSP, p53 and pRb proteins. The prominent peaks were found for HSPs at fHSP ¼ 0.0195 and HSP, p53, pRb at f2 ¼ 0.4316.